This is a multidisciplinary research program, employing innovative analytical methods for the study of interrelated neurophysiological, biochemical, and pharmacological aspects of epilepsy. In the clinically oriented research, analysis of temporal variabilities and biorhythms of clinical and electrical epileptic activity over time examines therapeutic response in a parametric design as a function of epileptic class, drug levels, clinical seizure incidence, and epileptiform EEG activity. Design and application of computer-based systems to improve EEG detection, characterization, and quantification of the epileptic process is a major aspect of the research program, as is the design and application of multimicroprocessor-based systems for the cost-effective analysis of data from prolonged monitoring studies. A specically designed time-synchronized, polygraphic recording and video-tape system is utilized to evaluate the effectiveness of the ACTH fragment (4-9) in the treatment of infantile spasms and to determine if the effectiveness of ACTH is mediated via the adrenal axis or by direct action on the brain. Fundamental studies employ in vitro hippocampal-slice techniques to elucidate membrane and synaptic mechanisms in epileptogenesis and the mechanisms of action of anticonvulsant and convulsant agents. The influence of epileptic seizures on neurogenic control and metabolic exchange of the cerebral microvasculature is examined in pentylenetetrazol-induced seizures in the rat, and the pathophysiological mechanisms involved in the elaboration of clinical and electrical seizures are studied in a new generalized-epilepsy model.